Exosome-mediated cell-cell communication in Rett Syndrome Development of functional neuronal circuits requires a complex series of events involving coordinated communication between multiple cell types over multiple dimensions of space and time. Extracellular membrane vesicles (EMVs), specifically exosomes, may serve as a novel form of cell-cell communication during brain development. Exosomes can transfer bioactive lipids, proteins, and RNAs between cells without requiring direct contact between the donor and recipient cells. So far, no studies have demonstrated that exosomes play a role in brain development or that deficits in exosome signaling might underlie neurodevelopmental disorders such as Rett Syndrome. We propose to address these fundamental open questions regarding the potential role of exosomes in brain circuit development in Rett Syndrome and healthy neurons using both mouse and hiPSC models.